Thrombosis in a cardiovascular system, particularly, arterial thrombosis, venous thrombosis, and cardiac thrombosis cause many diseases such as stroke, heart attack, deep vein thrombosis, or a pulmonary embolism. Among others, acute thrombosis causing acute cerebral infarction has recently increased with the development of modern society and has become a major social issue.
Further, from an economic aspect, a total cost resulting from strokes reaches a range of ten billion dollars or more each year globally; for example, there are direct costs related to hospital expenses and nursing costs such as hospital stay, treatment by doctors and health professionals, medicine, home health costs, and other medical goods, and indirect costs such as productivity losses due to disease, productivity losses due to death, or the like.
Many attempts to prevent and treat stroke, which is a major social issue in health care, have been continuously developed for the last 60 years by many researches, and thus, angiography, heart valve prosthesis, computed tomography (CT), transcranial doppler (TCD), and so forth have been studied.
Recently techniques involving an injection of a thrombolytic agent such as a tissue plasminogen activator (tPA) to reduce neurobiological damage have begun to emerge.
In the case of Korea, it is reported that there are about hundred thousand people who have an acute stroke (about 80% of them have cerebral infarction), and approximately 3 to 4% of the patients are treated with tPA. Accordingly, the economic benefits Korea from using tPA are estimated to be about 20 billion won.
According to the NINDS tPA trial, i.e. in case of conventional intravenous thrombolytic treatment, it was determined that a probability that patients will live independently without other people's help is one out of every seven patients; moreover, it turned out to carry problems that patients only within 3 to 6 hours from the symptom onset can be treated.
The problems seem to result from the fact that intravenous thrombolytic therapy has a mild to moderate effect while the side effect of the treatment is not low; about 5 to 10% patients have cerebral hemorrhage, cerebral edema, or the like. Therefore, by increasing the effect of thrombolytic treatments and reducing the side effects, and by increasing the range of treatable patients, post-stroke recovery from initial deficit will be increased. Subsequent humanitarian benefits for patients and their families and consequent national and economic benefits will be great.
Iodine-based contrast agent used as a CT contrast agent could have side effects and toxicity, and these conventional CT contrast agents are not targeted to a specific disease; thus, it can't diagnose a disease unless there is tissue damage and in particular, there is no method of imaging a thrombus which is the cause of a cerebral infarction.
Recently, there have been studies using gold nanoparticles as a CT contrast agent. Since gold has higher molecular weight than iodine, and gold nanoparticles have about 2.65 times higher X-ray absorption coefficient per unit of weight than iodine (based on an X-ray intensity of 100 keV). Thus, gold nanoparticles are highly useful as a CT contrast agent. Moreover, gold nanoparticles are easy to control in terms of the modification of the size and surface characteristics. Furthermore, gold nanoparticles are biocompatible, thus they may well be utilized for developing biomedical techniques. In addition, using such optical properties as suppressing fluorescence would provide advantages in other fields of imaging.
In the monitoring of thrombus, since there is a problem that delayed treatment worsens stroke outcome, CT (particularly non-contrast CT) that allows a more rapid acquisition of brain images compared with MRIs, is widely used as an imaging tool for thrombus monitoring.
However, when non-contrast CT as described above is used, there are many cases that the location or a size of thrombi could not be determined. Thus, the following problems regarding the thrombus monitoring can occur: the determination of individual volume of a thrombolytic agent or the triage of interventional treatment (vs. pharmacologic treatment) is difficult, and thus a pre-determined fixed dose tPA protocol instead of tailored therapy is being used in clinic.
Although there is a method using MRI for non-invasive thrombus imaging, with no sacrifice of experimental animals, quantification is relatively difficult and the cost is relatively high compared with CT; a large size quantitative experiments are difficult to be performed using MR-based thrombus imaging Therefore, there is an urgent need for solving these problems.